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The paper deals with the construct of the meaningfulness of life. After reviewing major theoretical and methodological approaches a new definition of meaningfulness of life is presented, grounded in the theory of meaning. Five different meaning-based assessment methods of meaningfulness of life are presented, each with a definition, major findings, advantages and disadvantages: the subject’s meaning profile, an open-ended examination of the meaning of the meaningfulness of life, overall rating scale of the meaning of the meaningfulness of life, a dimensional questionnaire of the meaningfulness of life, and the four anchors of the meaningfulness of life. The interrelations of the five measures and the manner in which they complement one another in exploring the meaningfulness of life are described. The relations of meaningfulness of life with the individual’s cognitive, emotional and personality tendencies are presented. A special section presents findings in a sample of cancer patients. The conclusions concern the nature and the psychological role of meaningfulness of life.