The development of CD4+ T helper cells is determined by the set of transcription factors and the genes these transcription factors transcribe. In this review, we describe the basic nature of Th1, Th2, Th9, Th17, T-follicular helper (Tfh), gamma delta (γδ) T cells, and T-regulatory (Treg) cells subsets, their master regulator transcription factors and their corresponding signature cytokine production profiles. Cellular immunity plays important role during virus infection. Optimal immune response to viral infections require a gentle balance of effector responses to clear the infected cells and regulatory mechanism to prevent immunopathology. The behavior of the helper cells differs with each virus–while in some cases, the response is beneficial; in other cases, it is harmful. We discuss the protective and pathological role of T cell immunity against influenza A virus (IAV), respiratory syncytial virus (RSV), immunodeficiency virus type 1 (HIV-1), and hepatitis B virus (HBV) infection.