Screening often leads to finding conditions that are not at the stage or level that would classify them as disease but, at the same time, are not at a stage or level at which people can be declared entirely disease free. These "in-between" states have sometimes been designated as "predisease." Examples include precancerous lesions, increased intraocular pressure ("preglaucoma"), prediabetes, and prehypertension. When the goal of preventing adverse health outcomes is kept in mind, this review poses the idea that "predisease" as a category on which to act makes sense only if the following 3 conditions are met. First, the people designated as having predisease must be far more likely to develop disease than those not so designated. Second, there must be a feasible intervention that, when targeted to people with predisease, effectively reduces the likelihood of developing disease. Third, the benefits of intervening on predisease must outweigh the harms in the population. A systematic review of screening guidelines (published in 2003-2010) for 4 sample conditions (cervical cancer, glaucoma, diabetes, and hypertension) is included to assess whether they address these issues, followed by a discussion of the framework questions as they pertain to each condition.