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Cacao (Theobroma cacao L.) is a tropical perennial crop which is of great economic importance to the confectionary industry and to the economies of many countries of the humid tropics where it is grown. Some recent studies have suggested that climate change could severely impact cacao production in West Africa. It is essential to incorporate our understanding of the physiology and genetic variation within cacao germplasm when discussing the implications of climate change on cacao productivity and developing strategies for climate resilience in cacao production. Here, we review the current research on the physiological responses of cacao to various climate factors. Our main findings are as follows: (1) water limitation causes significant yield reduction in cacao, but genotypic variation in sensitivity is evident; (2) in the field, cacao experiences higher temperatures than is often reported in the literature; (3) the complexity of the cacao/shade tree interaction can lead to contradictory results; (4) elevated CO2 may alleviate some negative effects of climate change; (5) implementation of mitigation strategies can help reduce environmental stress; and (6) significant gaps in the research need addressing to accelerate the development of climate resilience. Harnessing the significant genetic variation apparent within cacao germplasm is essential to develop modern varieties capable of high yields in non-optimal conditions. Mitigation strategies will also be essential, but to use shading to best effect shade tree selection is crucial to avoid resource competition. Cacao is often described as being sensitive to climate change, but genetic variation, adaptive responses, appropriate mitigation strategies and interactive climate effects should all be considered when predicting the future of cacao production. Incorporating these physiological responses to various environmental conditions and developing a deeper understanding of the processes underlying these responses will help to accelerate the development of a more resource use efficient tree ensuring sustainable production into the future.