MAGI-1 is a critical cellular scaffolding protein with over 110 different cellular and microbial protein interactors. Since the discovery of MAGI-1 in 1997, MAGI-1 has been implicated in diverse cellular functions such as polarity, cell-cell communication, neurological processes, kidney function, and a host of diseases including cancer and microbial infection. Additionally, MAGI-1 has undergone nomenclature changes in response to the discovery of an additional PDZ domain, leading to lack of continuity in the literature. We address the nomenclature of MAGI-1 as well as summarize many of the critical functions of the known interactions. Given the importance of many of the interactors, such as human papillomavirus E6, the Coxsackievirus and adenovirus receptor (CAR), and PTEN, the enhancement or disruption of MAGI-based interactions has the potential to affect cellular functions that can potentially be harnessed as a therapeutic strategy for a variety of diseases.