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Cancer remains one of the major threats to human health and one of the deadliest diseases worldwide [1]. Therapy failure and consequent cancer relapse are the main factors contributing to high cancer mortality, making it crucial to find and develop new therapeutic options. Over the last few decades, natural products became one of the key drivers in the drug development of innovative cancer treatments [2]. In opposition to drug development from terrestrial resources, the marine environment only recently emerged as a prolific source of unparalleled structurally active metabolites [3]. Due to their excellent scaffold diversity, structural complexity, and ability to act on multiple cell signaling networks involved in carcinogenesis, marine natural products are ideal candidates to inspire the development of novel anticancer medicines [4, 5]. The Special Issue “Marine Natural Products as Anticancer Agents”(https://www. mdpi. com/journal/marinedrugs/special_issues/AnticancerAgents (accessed on 15 June 2021)), gathered nine publications, including a review, a communication, and seven research articles, providing an excellent overview of the chemical richness offered by different marine organisms. Indeed, sponges, myxobacteria, fungi, and soft corals, provide essential scaffolds at the origin of the synthesis and molecular modeling of new anticancer drugs. Marine natural compounds or derived products described in this Special Issue belong to distinct chemical classes, including terpenoids, alkaloids, cyclodepsipeptides, polyketides, and hydroxyphenylacetic acid derivatives. These compounds modulate cancer cell mechanisms in vitro and in vivo in …