Molluscum contagiosum (molluscum) is a common skin condition, especially in children, yet treatment approaches by US health care practitioners vary widely. A dearth of clinical data from large, well-controlled studies has resulted in significant gaps in knowledge, including treatment guidelines and algorithms. As of this writing, there are no FDA-approved treatments for molluscum. The objective of this review is to provide practitioners with expert, evidence-based information and guidance about treatment approaches for, and the special circumstances faced by, patients with molluscum. To this end, a group of five pediatric and adult dermatologists collectively identified treatments and special considerations they felt were most commonly used to treat molluscum. Hence, in the first part of the review, seven treatment approaches identified as the most important to review (e.g., curettage, cantharidin) are discussed in terms of their mechanisms of action, supporting clinical data, and rationale for use. Each treatment approach concludes with a “clinical pearls” section, which summarizes the group’s experiences with the treatment. In the second part, five special considerations (e.g., atopic dermatitis, skin of color) are discussed with supporting clinical data and are also followed by a “clinical pearls” summary. J Drugs Dermatol. 2021;20(11): 1185-1190. doi:10.36849/JDD.6383.