Thrombocytopenia is defined by clinical characteristics and pathophysiologic mechanisms. The patient with thrombocytopenia often presents diagnostic and management challenges simultaneously. The differential diagnosis is broad because the disorders leading to thrombocytopenia are diverse, with failed production at one extreme and accelerated destruction at the other. Reviewed in terms of diagnosis and therapy are pseudothrombocytopenia, dilutional thrombocytopenia, and the three major mechanisms: decreased production, altered distribution, and increased destruction.