High-throughput technologies in combination with modern exciting advancements in mass spectrometry-based proteomics and data analysis pipelines have empowered comprehensive characterization of disease phenotypes and their mechanistic regulation by dietary agents and bioactive molecules at unprecedented dimensionality and resolution. Extra-ordinary breakthroughs in the field of nutrigenomics have leveraged our understanding altogether to a new level of maturity. Interdisciplinary researchers have extensively analyzed health promoting and pharmacologically significant properties of garlic (Allium sativum). Importantly, garlic and its biologically active chemicals targeted oncogenic signaling cascades. In this mini-review we have attempted to summarize how garlic and its bioactive constituents regulated signal transduction cascades in cell culture studies and tumor-bearing mice.