The phosphatidylinositol-3-kinase (PI3K) pathway is ubiquitous to multiple cellular processes and is intricately implicated in lymphomagenesis. The development of PI3K inhibitors has broadened treatment options for relapsed and/or refractory follicular lymphoma (FL) and currently three PI3K inhibitors have been approved in the third-line setting for FL, including idelalisib (oral), duvelisib (oral), and copanlisib (intravenous), with other agents under investigation. In this review, we discuss the clinical advance of copanlisib through preclinical to Phase III trials, its unique cellular targets and side effect profile that have poised it as a safer and equally efficacious option when compared to the older-generation oral PI3Kis, and its utility to the clinician as part of the therapeutic armamentarium for relapsed and/or refractory FL.