The widespread use of molecular biological tools has led to a pronounced increase in the number of signals that are now implicated in the controls of food intake and body weight. However, a complete understanding of the roles of these multiple signals requires that we assess how they interact with one another to alter ingestive behavior. Although many such experiments are being conducted, the methods employed to delineate these interactions are often fraught with interpretive difficulties. The purpose of this article is to explore these difficulties and offer practical advice for minimizing these issues in experiments that seek to explore the important interactions among these signals. In particular, the issues of additive vs. nonadditive results, the use of sub- or suprathreshold dose combinations, and the choosing of multiple-dose analyses are all addressed. Furthermore, the possibilities of using intake measures other than cumulative intake and complementary nonbehavioral endpoints are encouraged.