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This article delineates a comprehensive approach to play therapy in work with children with cancer. It considers different psychological needs experienced by the patient in connection with significant moments related to cancer treatment and the psychological tasks it involves. Different therapeutic aims are presented, and the therapeutic components related to each are described in detail. The therapeutic aims approached by play therapy are reality testing and ego strengthening, unveiling and working through of unconscious conflicts related to disease, and defense maturation. Therapeutic components leading to the attainment of those aims include the provision of realistic information about diagnosis and treatment by means of play, the use of play as a space for containment, the detection and interpretation of unconscious anxieties and defenses within play, and the exploration and trial of adaptive defenses in the face of illness-related anxiety. Implications of this approach in terms of the precision and flexibility of therapeutic actions and the diversity of roles played by the therapist are discussed.