Objective: To review the efficacy, safety, and role of lenacapavir (LEN) in the treatment of HIV-1 infection. Data Sources: A literature search was performed using PubMed and Google Scholar (through March 2023) with the search term LEN and GS-6207. Other resources included abstracts presented at recent conferences, the manufacturer’s Web site, and prescribing information. Study Selection and Data Extraction: All relevant articles, trial updates, and conference abstracts in the English language were included. Data Synthesis: Lenacapavir represents a new class of antiretrovirals (ARVs) with a novel mechanism of action as a capsid inhibitor and a unique twice-a-year subcutaneous administration schedule. Lenacapavir when combined with other ARVs has proven to benefit heavily treatment-experienced (HTE) patients with HIV-1 infection in achieving viral suppression and immune restoration. Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs: Lenacapavir is a new treatment option that patients who are HTE can consider adding as part of an ARV regimen. Conclusions: Lenacapavir is an effective and well-tolerated option for HTE patients which is a valuable addition to the arsenal of ARVs.