In veterinary and medical sciences, immunomodulation is an area wherein extensive studies have been conducted to devise methods to improve disease resistance as well as to prevent or control immune disorders of host by optimum regulation of the immune system. Today, most infectious diseases of man and animals are treated and controlled mainly by using broad-spectrum antibiotics and vaccines. However, the antibacterial agents are becoming increasingly ineffective due to rapid emergence of resistant microbial strains. So, there is high requirement for novel and improved alternative therapeutic and prophylactic strategies to manage several diseases which are flaring at alarming pace because of the increase in international traffic, globalization and changing food habbits. Immunomodulation is focused on manipulation of immune system to control the infections and other adverse health effects with precise regulation to avoid any complications while suppressive or potentiating efforts are made to benefit the animal and human health. The main aim of this review is to give a closer insight into the potential immunomodulatory molecules, synthetic and natural, that are capable of modifying the immune responses including conventional and novel immunomodulators like adjuvants, cytokines, hormones, glucocorticoids, host defense peptides, microbial products, toll like receptors, synthetic compounds, probiotics, nutrients, vitamins, minerals, herbs, panchgavya, polysaccharides, helminths, vaccines and others. These immunomodulatory regimens could successfully offer the health industries with the most natural methods for enhancement of disease resistance, boosting vaccination immunity, and prevention of various infections, disorders, cancer and stress related diseases. The updated information will be highly useful for scientists, veterinary/medical professionals, pharmaceutical industries, livestock and poultry industry to create a healthier future for people and their companion animals.