Retiform purpura consists of branching purpuric lesions caused by a complete blockage of blood flow in the dermal and subcutaneous vasculature. The differential diagnosis for retiform purpura is broad, including vasculitides of the small and medium vessels as well as microvascular occlusion due to thrombotic, infectious, and embolic phenomena. Determining the etiology of this important dermatologic sign can be a diagnostic challenge; however, an organized approach can improve the speed and accuracy of diagnosis and identify an effective treatment. This review focuses on early recognition, evaluation, and treatment of hospitalized patients with retiform purpura. Specifically, vasculitis, protein C and S deficiencies, heparin necrosis, warfarin necrosis, antiphospholipid antibody syndrome, disseminated intravascular coagulation, cryoglobulinemia, calciphylaxis, and cholesterol embolization syndrome will be discussed in detail. These conditions are commonly seen in consultative dermatology and can have multiorgan involvement, complicated laboratory evaluation, and long-term therapeutic implications.