Many of the complications experienced by patients undergoing hemodialysis can be attributed to their altered host defenses. Increased cutaneous staphylococcal carriage along with repeated intravascular cannulation and defective mucocutaneous barriers lead to frequent invasion by infectious agents. Pathogens encounter granulocytes with subnormal locomotion, phagocytosis, and intracellular killing. Depressed cell-mediated immunity may be explained by shortened lymphocyte survival, lymphopenia, inhibition of lymphocyte transformation, and suppressor T-cell activity. This is manifested by cutaneous anergy, prolonged graft survival, altered tumor surveillance, and abnormal responses to hepatitis B and tuberculosis. Host interaction with the hemodialysis membrane leads to cellular disruption, which may induce autoantibodies. Activation of the alternate complement pathway during hemodialysis leads to granulocyte sequestration in small vessels, specifically within the lungs. These hemodialysis-induced alterations along with the manifestations of underlying chronic renal insufficiency may obscure clinical evaluation of these patients.