Background: The peak age of onset of schizophrenia is during late adolescence and young adulthood. Early onset schizophrenia—that which occurs prior to age 18—is more likely to be treatment resistant. The management of schizophrenia in the adolescent patient poses many challenges.Methods: We present a complex case of a patient diagnosed with schizophrenia when she was 16 years old. The patient initially developed symptoms of depression and obsessions after stressful life events. The OCD and depressive symptoms remitted partially with medications. She also had short stature and delayed puberty, possibly related to growth hormone deficiency. Results: The patient’s psychotic illness did not respond well to typical and atypical antipsychotics, but she improved dramatically on clozapine. Treatment was augmented with estrogens. However, she had persistent cognitive deficits that were quite disabling and interfered with academic functioning. Conclusion: The case illustrates how multiple factors – psychosocial and hormonal -- might have been involved in the development of schizophrenia in this adolescent and the challenges of treatment resistant schizophrenia. In particular, we discuss the possibility of a link between delayed puberty and schizophrenia and raise the question of whether growth hormone deficiency could make adolescents susceptible to early-onset schizophrenia.