Randomized, parallel group clinical trials often require large groups of patients; this is expensive and takes time. A randomized cross-over trial can be an efficient and more affordable alternative. A cross-over design can be used to study chronic disorders in which treatments have temporary effects. Participants receive all treatments in consecutive periods and outcomes are measured after every period. In general, only a quarter of the total group size is needed for cross-over studies compared with parallel group studies. Results can be affected by period-effects and carry-over-effects, which can be prevented through randomization and a wash-out period of sufficient length. The dropping-out of participants has more negative consequences for cross-over studies than for parallel group studies.