Coffee is one of the most popular and consumed beverages worldwide, and caffeine is its best-known component, present also in many other beverages (tea, soft drinks, energy drinks), foodstuffs (cocoa, chocolate, guarana), sport supplements and even medicines. Besides caffeine, many other components, either beneficial for health (chlorogenic acids, polyphenols, diterpenes, micronutrients, melanoidins, fiber) or not (lipids in unfiltered coffee, or acrylamide resulting from coffee bean roasting), are present in coffee. Just to illustrate the scientific interest of coffee and caffeine, when these terms are combined in PubMed (as “coffee OR caffeine”), almost 50,000 papers can be retrieved (as of 10 August 2021). Furthermore, from 2000 to 2020, the number of manuscripts published per year has more than doubled (from 972 to 2601). Within this context of increasing interest in the topic, the Special Issue (SI) on “Coffee and Caffeine Consumption for Human Health” has collected twenty-one manuscripts (five narrative reviews and sixteen original articles, including two meta-analyses).