Background and objectives: Major Depressive Disorder (MDD) is a recurrent, chronic, and debilitating mental illness which demands daily management using self-management strategies (SMS). Much of the literature on self-management is derived from research focused on Western culture. Less is known about how people self-manage their MDD in other cultures. Hence, a qualitative study was designed to understand how women in Pakistan self-manage their recurrent MDD. The aim of this paper is to describe a set of findings pertinent to the role of religion/spirituality in Pakistani women’s experiences with recurrent depression and their use of religious/spiritual SMS that were extracted from results of a larger study. Population: A purposive sample of 10 Pakistani women living in Karachi, Pakistan and seeking treatment for MDD from the psychiatric outpatient clinic at a private tertiary care hospital in Karachi were included in the study. Methods: A qualitative, descriptive study was conducted using the data from a total of 27 interviews. ATLAS.ti was used to organize, manage, and qualitatively and thematically code and analyze the transcribed interview data. Results: Three major themes emerged from the data. The first theme was the experience of depression. The women’s experience of depression was integrated with their individual religion/spirituality. They all shared a polarized perspective, i.e. depression as positive as well as painful. The second theme was strategy selection. Women unanimously reported that faith in God, family and social network structure, and broader cultural practices influenced their selection of religious/spiritual focused strategies. The third theme was religious/spiritual SMS. Women identified (a) having faith in God, and (b) ways of connecting with God as their religious/spiritual focused strategies. Having faith in God was not only viewed as an influencing factor but also as a strategy. Women shared four ways through which they connected with God (i) performing prayers, (ii) reciting the holy Qur’an, (iii) talking to God, and (iv) performing a Pilgrimage. Interpretation and Conclusions: Religion and spirituality are the critical lenses through which Pakistani women understand their illness and make decisions about how to manage their MDD. Since self-management occurs within a socio-cultural context, it is imperative for nurses to understand not only the religious and spiritual perspectives but also socio-cultural perspectives to facilitate and support women’s efforts to self-manage their MDD.