The complement cascade is a key component of our body’s innate immune system, protecting us from infection even at our first encounter. To act in this way complement must be nonspecific and strongly proinflammatory, meaning it also has the potential for adverse outcomes from off-target complement activation. In this webinar, we will work to demystify the complement cascade, clarify the pathways, and review which components belong to which pathway. Once we have this shared understanding, we will be able to discuss the basic functions of complement and how those functions can turn on the host and cause adverse events when the cascade is inappropriately activated. This discussion will include an analysis of the biomarkers that are useful to investigate adverse complement activation down to the specific pathway level and go further to share what is important to know when considering measuring complement, prospectively or retrospectively. We will also review what is known about complement-mediated toxicities for specific test article classes and the differences in those reactions in different species.