The immunocompromised host's susceptibility to infections often present a difficult diagnostic challenge to the physician. A working knowledge of the host immune defenses and microbiologic complications that can occur when these functions are compromised provides a more focused framework for further evaluation and management. Infections in these patients are often morbid and life-threatening, creating an urgent need for prompt diagnosis. The skin may manifest the first clue(s) of a serious underlying infection. Appropriate workup and diagnosis of cutaneous lesions provide an expeditious, noninvasive, and potentially life-saving approach to the immunocompromised host with a dermatologic infection.