Chronically ill patients with neurodegenerative, central nervous system symptoms and neurobehavioural symptoms commonly have systemic and central nervous system bacterial and viral infections. These may include, Mycoplasmas, Chlamydia pneumoniae, Herpes viruses, Co- infections, Retrovirus, Cytomegalovirus, Lyme and many other bacterial and viral infections. The role of these pathogeneses play a large part in chronic illnesses from chronic inflammation to debilitating fatigue. Recent data suggests that these usually dormant bacterial and viral pathogeneses play a role in difficult cases that do not resolve on current protocols. Immune suppressed patients can test with high positive titers to one or several. Unraveling the layers of infection can put the patient on the road to their recovery.