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Immunomodulating monoclonal antibodies are a relatively new addition to the armamentarium of cancer therapeutics and have been shown to improve clinical outcomes in patients with various hematologic malignancies. Because of their targeted nature, these agents are often believed to be less immunosuppressive than standard cytotoxic chemotherapeutic agents. A clear causal association between an immunomodulating therapy and its infectious sequelae is often difficult to discern because of the burden of comorbid illness, intrinsic immunosuppression from the underlying malignancy, use in the salvage setting, and prior and concomitant use of immunosuppressive agents in this patient population. This article evaluates better-established and anecdotal infectious complications associated with major immunomodulating therapies used in hematologic malignancy and hematopoietic stem cell transplantation, including rituximab, alemtuzumab, gemtuzumab ozogamicin, infliximab, dacluzimab, and basiliximab.