Coffee, a complex brew containing hundreds of biologically active compounds, exerts potent effects on long-term human health. Recently, a plethora of studies have been published focusing on health outcomes associated with coffee intake. An inverse association between coffee consumption and all-cause mortality has been seen consistently in large prospective studies. Habitual coffee consumption is also associated with lower risks for cardiovascular (CV) death and a variety of adverse CV outcomes, including coronary heart disease (CHD), congestive heart failure (HF), and stroke; coffee’s effects on arrhythmias and hypertension are neutral. Coffee consumption is associated with improvements in some CV risk factors, including type 2 diabetes (T2D), depression, and obesity. Chronic coffee consumption also appears to protect against some neurodegenerative diseases, and is associated with improved asthma control, and lower risks for liver disease and cancer. Habitual intake of 3 to 4 cups of coffee appears to be safe and is associated with the most robust beneficial effects. However, most of the studies regarding coffee’s health effects are based on observational data, with very few randomized controlled trials. Furthermore, the possible benefits of coffee drinking must be weighed against potential risks, which are generally due to its high caffeine content, including anxiety, insomnia, headaches, tremulousness, and palpitations. Coffee may also increase risk of fracture in women, and when consumed in pregnancy coffee increases risk for low birth weight and preterm labor.