What is Zoloft? Zoloft (sertraline) is an antidepressant in a group of drugs referred to as selective serotonin reuptake inhibitors (SSRIs). The way sertraline works is still not fully clear. It is thought to positively affect communication between nerve cells in the central nervous system and restore chemical balance in the brain. Zoloft is used for treating panic disorders, post-traumatic stress disorder, and premenstrual dysphoric disorder (PMDD) depression, obsessive-compulsive disorder….