Coffee is one of the most widely and frequently consumed beverages worldwide. Although it is often linked with caffeine, coffee is a complex mixture of >1000 bioactive compounds, many of which have antioxidant capacity including polyphenols, diterpenes, melanoidins, and various minerals.1,2 Coffee has been shown to have anti-inflammatory and insulin-sensitizing properties and is associated with lower levels of inflammatory cytokines3–5 and C-peptide (Figure 1A).1,6 Owing to these broad potential mechanisms and wide-ranging bioactive compounds, coffee drinking has been investigated in relation to a variety of health disorders, with beneficial effects consistently reported for the metabolic syndrome and diabetes, liver and digestive disorders, cardiovascular disease, and overall mortality.7 In 2017, 3 large-scale cohort studies from the United States and Europe reported that coffee drinkers had significantly lower risk of premature death from a variety of causes.8–10 Owing to its effects on gut motility and the gut microbiome (Figure 1A), there has been particular emphasis on the relationship between coffee and digestive tract disorders, and there is accumulating evidence to support a specific link between coffee and colorectal cancer. Indeed, a 2011 meta-analysis of 15 prospective studies revealed that coffee consumption was inversely associated with risk of developing colorectal cancer.11