The potential for the use of antimicrobial peptides (AMPs) as anticancer agents has garnered much interest because of their selective cytotoxicity to tumor cells and ability to evade multidrug resistance mechanisms. AMPs are shorter cationic amphiphilic molecules, part of our innate immune system, with direct membrane-disruptive activity and immunomodulatory effects. Anticancer peptides (ACPs) can be derived from natural biophysical sources or synthetically engineered, taking advantage of the unique biophysical properties of cancer cell membranes to exert their anti-tumor activities rapidly and often without significant effects on normal tissues. Advances in peptide engineering, such as D-amino acid substitution, cyclization, and PEGylation, combined with nanocarrier systems, have provided opportunities to improve peptide stability, bioavailability, and delivery to targeted sites. Studies in preclinical and clinical models show promise, indicating that AMPs and ACPs can induce immunogenic cell death, modify tumor microenvironments, and be used in combination with more conventional therapies. While the promise of AMPs and ACPs as relatively novel cancer therapeutics is substantial, challenges such as proteolytic degradation, dose-dependent toxicity, costs for production, and regulatory hurdles are notable. This review organizes the current literature on classification, mechanism(s) of action, delivery strategies, preclinical and clinical data, and provides areas for future work to improve and help speed their clinical translation as new cancer therapies.