The world of work that adolescents with ASD will participate in after they leave high school will be very different from the work context most of today’s teachers have experienced. Changing global economic and work structures are creating the need to equip young people to “design” their own careers. This chapter will provide direction and support to implement strategies to enable youth with ASD to identify career preferences and interests, to self-regulate job and career actions, and to construct a plan for achieving a fulfilling career. Strategies to promote effective transition planning for 21st century work-life skills are discussed.