Historically, hydration research reflected critical issues of the day. War, illness, surviving a shipwreck or time in the dessert, supplying fall-out shelters, and space exploration drove hydration research in the first half of the 20th century. The fitness revolution of the 1970s spurred research on dehydration in physically active people and athletes. The 1990s introduced the “fluid/disease relationship.” What will be the driving force behind hydration research in the 21st century? Where are the gaps in our knowledge? This review provides an overview of issues pertinent to determining future directions in hydration research.