This article discusses the use of topical and systemic therapy in the management of advanced periocular tumours. It focuses on those that have gained United States Food and Drug Administration approval; namely imiquimod, vismodegib, sonidegib, pembrolizumab and cemiplimab. Imiquimod is a topical therapy, whereas the rest are systemic. The indications for these medications are locally advanced and metastatic BCCs or SCCs that are not amenable to resection or radiotherapy. Many of the research articles in the literature focus on carcinomas located in other regions. This paper highlights those articles demonstrating outcomes for tumours in the periocular area although the number is limited and the sample size usually small. Imiquimod remains the better tolerated of the medications discussed and this is likely due to it being topical. The other medications have significant side-effects (including muscle spasms, alopecia and taste disorders) that often result in discontinuation. The moderate response rate has limited their widespread use so far and the development of more topical treatment may be the way forward in these difficult to treat cases.