As average life expectancy increases, the incidence of many malignancies continues to rise. Fortunately, cancer-directed therapies have expanded over the last few decades with the addition of immunotherapy and targeted therapies to conventional chemotherapy. Consequently, clinical outcomes for most malignancies have improved. However, these treatment regimens are associated with the costs of adverse effects. Dermatologic toxicity resulting from cancer-directed therapies ranges from mild nonspecific rash to life-threatening severe adverse events like toxic epidermal necrolysis. The incidence and the severity of these adverse drug effects vary significantly. While some skin manifestations are nonspecific, others have distinct features depending on the triggering agent. Diagnosis of cutaneous reactions is primarily based on clinical presentation, although there may be a need for comprehensive dermatologic evaluation, including skin biopsies. Management of these reactions varies based on the type and the severity of the skin reaction and may sometimes necessitate interruption, or discontinuation of cancer-directed therapy. Within the rapidly evolving cancer therapies, multidisciplinary approach in evaluation and management of the cutaneous manifestations become crucial.