While the importance of mutualisms across the tree of life is recognized, it is not understood why some organisms evolve high levels of dependence on mutualistic partnerships, while other species remain autonomous or retain or regain minimal dependence on partners. We identify four main pathways leading to the evolution of mutualistic dependence. Then, we evaluate current evidence for three predictions: ( a ) Mutualisms with different levels of dependence have distinct stabilizing mechanisms against exploitation and cheating, ( b ) less dependent mutualists will return to autonomy more often than those that are highly dependent, and ( c ) obligate mutualisms should be less context dependent than facultative ones. Although we find evidence supporting all three predictions, we stress that mutualistic partners follow diverse paths toward-and away from-dependence. We also highlight the need to better examine asymmetry in partner dependence. Recognizing how variation in dependence influences the stability, breakdown, and context dependence of mutualisms generates new hypotheses regarding how and why the benefits of mutualistic partnerships differ over time and space.