Of Two Minds follows the challenging relationship between two sisters, Billie Clark (Kristen Davis) and Elizabeth 'Baby' Clark (Tammy Blanchard). Baby suffers from schizophrenia and lives with their mother who helps care for her while Billie settles down happily with her family. When their mother has a sudden stroke, Billie takes on the responsibility of caring for her younger sister and moves into their childhood home along with her husband (Joel Gretsch) and two teenage children (Mackenzie Aladjem and Alex le Bas). Baby's swiftly changing moods and uncontrollable episodes bring high levels of stress to the family while they try to adjust to the new living arrangements until a disturbing incident occurs between Billie's son and Baby. Afterwards, it is clear to Billie that she is not in a position to handle Baby's illness and is faced with a difficult decision on how to properly care for her sister while she considers what is best for Baby and for her family.<ref name=lifetimeabout />