The Importance of a Malware Free System
Malware has malicious intent and can potentially: 
- View and take snapshots of the desktop.
- Peruse files and folders.
- Gain access to protected data when decrypted.
- Exfiltrate, corrupt or destroy data (particularly financial and personal information).
- Damage operating system functionality.
- Encrypt the contents of a drive(s) and demand payment for decryption (ransomware).
- Display unwanted advertising.
- Install unwanted software.
- Install persistent rootkits or backdoors.
- Track browsing and other behaviour.
- Remotely turn on webcams and microphones.
- Create "zombie" computers which form part of a botnet for spam email, DDOS attacks or the hosting of illicit / illegal material.
- Record everything a user types, sends and receives.
The Utility of Antivirus Tools
Antivirus products and personal firewalls are not drop in solutions for a secure host. Malware can often stay undetected and evade scans, while application level personal firewalls are often circumvented.  Polymorphic code and rootkits essentially render antivirus products helpless.  
Antivirus tools are actually worse than useless. In the case of sophisticated and targeted attacks, the antivirus software can serve as a pathway to exploiting a system's kernel, since they almost always run with administration level privileges.  Antivirus software also harms privacy by sending system files back to the company servers for analysis. The software also actively conducts man-in-the-middle attacks on secure SSL connections, enabling very sensitive information to be viewed. 
Preventing Malware Infections
The optimal scenario is to avoid infection by malware in the first place. Once malicious code has accessed a system, it is next to impossible to contain. Sensible steps include: hardening the operating system, carefully vetting programs and files that are retrieved from the Internet, and using hypervisors (virtualizers) to isolate software that processes untrusted data.
Detecting Malware Infections
Detecting off-the-shelf (standardized) malware is a very hard problem and conceptually a lost cause. If uncustomized malware is widespread enough, then it has a chance of being detected by a technician. Tailored malware might also get detected by a technician, but the likelihood is low unless they are lucky or gifted.
Non-technical users do not have many good options. They can either:
- Spend a few years to rapidly increase their knowledge base of operating systems, network protocols, package analysis, programming, disassembly etc., and then try their luck.
- Pay exorbitant sums to a technician to try and find system malware, even though there is no certainty of success.  
- Or seek the voluntary assistance of a technician to find malware, if they are both a high value target and have a reasonable rationale for why they are likely compromised. 
Once a user is infected with very sophisticated malware that modifies low-level firmware, it is extremely difficult to detect in almost all cases.
Firmware infections should not be confused with hardware/circuit trojans, which are malicious modifications made to machine components during the manufacturing process. Despite their sophistication, circuit trojans are not immune to detection. 
Virtualizers and Hardware Compromise
Virtualizers like Qubes, VirtualBox and KVM cannot absolutely prevent the compromise of hardware. Running all activities inside VMs is a very reasonable approach. However, this only raises the bar and makes it more difficult and/or expensive to compromise the whole system. It is by no means a perfect solution.
No distribution of Linux, BSD, Xen or any other variant can solve the issue of needing to dispose of potentially infected hardware. Hardware-specific issues can really only be fixed at the hardware level. At best, software interventions can only provide workarounds.
The Promise of Libre Firmware
The problem is no hardware exists that consists of entirely Libre firmware. It is very difficult to analyze the firmware of hardware, wipe potentially compromised versions, or overwrite firmware with a most-likely-clean version.
Even if a user wholly depended on Libre firmware, this would only make verification easier but it could not stop infection. Disassembling hardware components -- BIOS, disk controllers, CPU, Intel AMT and so on -- and flashing them with clean versions offline is extremely difficult. It is simply cheaper and more convenient to buy new hardware.
The bundling of undesirable anti-features like DRM in closed firmware is further evidence that Libre firmware is needed, in addition to Libre hardware designs.
- A botnet author brags in this thread of writing unbeatable malware and trolling antivirus vendors.
- The salary costs for a security researcher / malware analyst over an extended period rule this out for most individuals.
- Only a select group of people fall into this group, for instance, whistleblowers targeted and infected by tailored viruses. Experts might be located who are willing to conduct analysis pro bono; later publicizing their findings for the public benefit.
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