Neonatal sepsis is the top cause neonatal mortality accounting for 36% of neonatal deaths followed by prematurity (28%) and birth asphyxia (23%) as leading causes of neonatal mortality. Recently the global burden of disease ( GBD) study 2016/2017 estimated 1.3 million annual incident cases of neonatal sepsis worldwide resulting in 203000 sepsis attributable deaths. Neonatal sepsis has resulted in an estimated economic burden of up to $469 billion in LMICs. It is very critical to reduce the prevalence of neonatal sepsis with appropriate preventive strategies, early intervention and prompt management of suspected cases keeping the suspicion index high. There are definitely challenges in LIMCs like Pakistan in managing neonatal sepsis both at community and hospital levels which need to be addressed with evidence based interventions. The problem of emergence of resistant organisms causing neonatal sepsis in NICU settings is a definitely challenging scenario for neonatologists in developing countries. However, with judicious application of scientific and evidence based interventions both at community and hospital settings coupled with introduction of appropriate antimicrobial therapy and various adjunctive therapies would go a long way in reducing neonatal morbidity and mortality due to neonatal sepsis.