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Inhibitors of BRAF and the downstream signaling protein MEK have improved outcomes for patients with BRAF-mutant advanced malignant melanoma. Despite their ease of administration, these oral therapies pose adherence challenges.This article aims to increase awareness of causes of nonadherence to oral targeted therapies in advanced malignant melanoma and to provide oncology nurses with strategies to address these nonadherence issues.Members of the Melanoma Nursing Initiative explored issues related to adherence to targeted therapies in advanced malignant melanoma. The current literature and clinical experience were reviewed.The authors present a care step pathway focused on increased patient engagement and rapid identification and optimal management of toxicities to avoid toxicity-related nonadherence. Other causes for nonadherence and employment of individualized strategies to support patient adherence are addressed.