Through a concrete case, we discuss the main published protocols to initiate methadone and illustrate the advantages and disadvantages of rapid or gradual initiation and on-demand or fixed doses with rescue doses. Daily doses can vary widely depending on the protocol chosen. An on-demand administration could lead to an overdose as illustrated in our case. A better understanding of particularities and limitations of these protocols could lead to safer methadone initiation. Systematic comparison of different protocols and calculation of the daily dose should be a standard in clinical practice.