Immune dysregulation has been observed in the majority of the infective and non-infectious respiratory illnesses with impact on the natural course of illness in pediatric to geriatric age groups. Immune regulation between Th1 and Th2 is altered and reversal of proportion between these two differential cells and ultimately homeostasis, with predominance Th2 cells will increase susceptibility for recurrent illnesses; is typically documented in pediatric age groups with first respiratory infection during early neonatal period with respiratory viral etiologies. Apart from recurrent childhood infections, pediatric cases with immune dysregulation will have recurrent wheezing in childhood and are prone for development of childhood asthma in adolescent age groups; if immune dysregulation does not restore in time. In adults, respiratory illnesses due acute viral infective etiology will cause immune dysregulation as documented after coronavirus, influenza and respiratory syncytial virus infections. Immune dysregulation has also been documented in chronic respiratory illnesses such bronchial asthma, chronic bronchitis and COPD. Immune dysregulation will cause recurrent exacerbations in these inflammatory conditions. Pidotimod is an immunomodulator which will work as an immunostimulant molecule due to its unique pharmacological actions on antigen presenting cells, and have novel action on immune cell proliferation and differentiation. In spite of three decades of research of this novel drug Pidotimod, still; it is less used as of today for respiratory ailments in spite of need of a molecule with an immunomodulatory effect for prevention and or cure of illnesses; and modification of natural course of recurrent or relapsing course of chronic illnesses. COVID-19 pandemic has taught us many pathways of immune dysregulation which evolved during natural course of disease and now documented with respiratory viral illnesses such as RSV; and its long-term impact as long covid presenting due to immune dysregulation occurred as a natural course in recovered cases. It’s unclear whether long covid is reversible as of now, but the majority of symptoms have been resolved and shown response to versatile molecules such as steroid, multivitamins, L-arginine, Paxlovid, beta blockers with variable results and long-term outcomes. Pidotimod can be used in acute COVID-19 illness without pneumonia and comorbidities in stable cases in outdoor settings, and also; considered as potential option in long covid cases with recurrent respiratory infections. In this review we have discussed basic aspects of Pidotimod, and its role in immunomodulatory effects in acute and chronic respiratory illness which have shown positive outcomes.