Tardigrades are ubiquitous meiofauna that are especially renowned for their exceptional extremotolerance to various adverse environments, including pressure, temperature, and even ionizing radiation. This is achieved through a reversible halt of metabolism triggered by desiccation, a phenomenon called anhydrobiosis. Recent establishment of genome resources for two tardigrades, Hypsibius exemplaris and Ramazzottius varieornatus, accelerated research to uncover the molecular mechanisms behind anhydrobiosis, leading to the discovery of many tardigrade-unique proteins. This review focuses on the history, methods, discoveries, and current state and challenges regarding tardigrade genomics, with an emphasis on molecular anhydrobiology. Remaining questions and future perspectives regarding prospective approaches to fully elucidate the molecular machinery of this complex phenomenon are discussed.