Spanning 20 years and two continents, Mary and Max recounts the pen-pal relationship between two very different people: Mary Dinkle, a chubby, lonely eight-year-old living in the suburbs of Melbourne, Australia; and Max Horovitz, a severely obese, 44-year-old Jewish man with Asperger's syndrome living in the chaos of New York City. The film deals with themes including childhood neglect, friendship, addiction, alcoholism, recovery, the obscurity of life, teasing, loneliness, mental illness, autism (Asperger syndrome in particular), obesity, suicide, depression, isolation, and anxiety.