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Using this framework of uncertainty across the trajectory of caregiving through the end of life, variations related to the care recipient's illness trajectory will be illustrated. While the major transitions of the caregiving trajectory are explicated in the model, the course of the caregiving experience is affected by the illness trajectory of the care recipient. Particularly, the duration of phases and the progression or course of the trajectory change in response to the trajectory of illness. Consider the relatively even slope of decline experienced in amyotrophic lateral sclerosis (ALS) versus the slope of decline punctuated by periodic exacerbations through the course of organ failure, for example, congestive heart failure. These trajectories of illness influence the course of caregiving, and ultimately, the caregivers' sense of uncertainty at the end of life. The course and duration of the caregiving trajectory across four different illness trajectories (that is, cancer, organ failure, ALS, and frailty) are illustrated. The critical junctures or key transitions demarcating the phases of the trajectory are emphasized to help nurses identify behavioral markers of the progressive course of caregiving. As nurses become more aware of these critical transitions, they stand better prepared to intervene to support caregivers.