A Maternal and Child Health Surveillance System (MCHSS) was set up by the department of pediatrics and child health, Aga Khan University, Pakistan in peri-urban areas of Karachi to provide a platform for various research projects. It was established in five low-socioeconomic communities in a stepwise manner between 2003 and 2014. The total area currently under surveillance is 18.6 km2 covering a population of 302,944. We maintain a record of all births, deaths, pregnancies, and migration events by two monthly household visits. Verbal autopsies for stillbirths, deaths of children under the age of five years and adult female deaths are also conducted. For over a decade, the MCHSS has been a platform for a variety of studies describing the burden of various infectious diseases like typhoid, pneumonia and diarrhea, evaluation of effectiveness of various treatment regimens for neonatal sepsis, assessment of the acceptance of hospitalized care, determination of the etiology of moderate to severe diarrhea, assessment of burden and etiology of neonatal sepsis and a multi-center cohort study measuring the burden of stillbirths, neonatal and maternal deaths. More recently we have also established a bio-repository of the well-characterized maternal and newborn cohort. Through a well-established MCHSS, we aim to provide concrete evidence base to guide policy makers to make informed decisions at local, national, and international levels.