Assuming control over the allocation of patients to treatment conditions is a fundamental element of any comparative clinical trial. There are three critical considerations investigators must balance in choosing an allocation scheme: reducing bias in patient allocation, producing balanced patient groups across treatment arms, and reducing the likelihood of errors attributable to chance variation. The authors review the principles of three key approaches to the allocation of patients to conditions within clinical trials, and their respective advantages with regard to these critical considerations. These allocation methods include randomization, stratification, and patient-treatment matching. Randomization is fundamental to most clinical trials. Stratification is an advanced step in a systematic program of research investigating the efficacy and effectiveness of an intervention. If the trial has less than 100 per arm and there is a known prognostic factor, stratification is the best choice to ensure equal allocation across groups. Treatment matching (tailoring) attempts to match the most appropriate treatment to a specific patient based on a priori hypotheses. Two techniques used for exploring treatment matching are: patient typologies (patient profiling), and aptitude-treatment interactions. Additional details pertaining to the rationale for selecting among these various approaches to patient allocation is provided, and their methodology is summarized with specific consideration for their application within clinical trials of headache treatment.