Strategies abound for the setting of analytical goals in clinical chemistry. Many, especially those more recently proposed for particular clinical situations, are concerned with tests used in diagnosis. We suggest a general theory for the setting of goals in situations that specifically involve the monitoring of individuals. Goals are calculated from the formula CVA less than [(delta c 2/2Z2)-CVB2]1/2, where CVA is the analytical imprecision (as coefficient of variation, CV); delta c is the percentage change in serial results that is considered clinically significant; Z is the Z-statistic, which depends only on the probability selected for statistical significance; and CVB is the average inherent within-subject biological variation (as CV). Examples given show applications in hematology and in monitoring diabetes mellitus, chronic renal failure, and hepatitis. The derived goals are for total random analytical error (imprecision and intermittent systematic variation), and provide objective criteria that should be achieved in practice. The effect of analytical variability on both variability in test results and the probability that a stated change can be considered significant should be calculated whether or not the goals are attained.