Lisa's struggle with her weight begins as a child and significantly worsens after witnessing her brother's murder; now bedridden and unable to care for herself, she must lose the weight or she will never see her grandchildren grow up.

Born as "Matthew," Destinee never felt like she fit in; now, having come out as a 600-pound transgender woman, she likes her curves, but she will need to say goodbye to them if she wants to be approved to transition completely.

Octavia has been bedbound for nearly a year when she decides to make the trip to Houston to get help from Dr. Now, but when it turns out that her best friend is also her worst enabler, Octavia will have to choose between old habits and a new life.

Robin and her brother Chris are both obese and already lost a sibling to obesity; they plan to visit Dr. Now together when Chris suffers a stroke and can't go; Chris' son Garrett, already 600 pounds at age 20, is game to join the journey.