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The concept of alliance reflects the collaborative relationship between a clinician and a patient, defined as consisting of three elements: a) the agreement on the goals of treatment; b) the agreement on a task or series of tasks; c) the development of a bond. Although much of the theory and research on the alliance comes from the domain of psychotherapy, the concept is applicable to any practice involving a person seeking help and a socially sanctioned healer. An extensive research evidence suggests that the alliance (typically measured at the third or fourth session) is a robust predictor of the outcomes of various forms of psychotherapy, even when prior symptom improvement and other factors are considered. Both the clinician and the patient bring to the therapy situation different capacities to form an alliance. Factors concerning the patient include, among others, the diagnosis, attachment history and style, motivation, and needs for affiliation. However, the benefits of the alliance have been found to be mostly due to the therapist's contribution, in particular his/her facilitative interpersonal skills, including verbal fluency, communication of hope and positive expectations, persuasiveness, emotional expression; warmth, acceptance and understanding; empathy, and alliance rupture-repair responsiveness. Placebo studies have allowed to experimentally manipulate aspects of the relationship between a therapist and a patient in non-psychotherapy contexts. In these settings, two components of the relationship have emerged: an emotional one (involving being cared for and understood by the clinician) and a cognitive one (including the belief in the competence of the therapist to select and administer an effective treatment). Here we propose a model that describes three pathways through which the alliance creates benefits, named CARE (caring, attentive, real and empathic), EXPECTANCY, and SPECIFIC. Although research and clinical attention have mostly focused on the alliance between a clinician and a patient in face-to-face interactions, there is preliminary evidence concerning the alliance between patients and other clinic staff, systems of care, or the program in Internet-mediated services. These new research areas clearly require further development.