This chapter discusses the neurobiology of the experience of meaning and meaningfulness. Knowing the meaning of something is different from making fresh meaning. The left hemisphere seeks meaningful experiences and the meaning of life, but without letting go to the right, the source of new meaning, it may be stranded in meaninglessness. When we re-connect with our felt experience in the body, it feels meaningful, and then to express our meaning we need both hemispheres. Topics addressed include imagery, dreams, transpersonal experiences, and the transformation of the self in therapy. To be effective, therapy itself must be experienced as meaningful.