The incidence of oesophageal adenocarcinoma has risen rapidly over the past four decades. Unfortunately, treatments have not kept pace; unless their cancer is identified at a very early stage, most patients will not survive a year after diagnosis. The beginnings of this widespread problem were first recognized over 25 years ago, yet rates have continued to rise against a backdrop of much improved understanding and management of oesophageal adenocarcinoma. We estimate that only ∼7% of the 10,000 cases of oesophageal adenocarcinoma diagnosed annually in the USA are identified through current approaches to cancer control, and trace pathways by which the remaining 93% are 'lost'. On the basis of emerging data on aetiology and predictive factors, together with new diagnostic tools, we suggest a five-tier strategy for prevention and control that begins with a wide population base and triages individuals into progressively higher risk strata, each with risk-appropriate prevention, screening and treatment options.