A high-resolution focused ion beam, at ~ nanometer or much finer scales (toward atomic size), has merits to push the envelope of critical applications in diverse areas. Toward this end, examples of several intriguing emerging applications include tailoring material properties through ultra-precise manipulations of atoms/molecules, fine-scale imaging revealing compositional maps in objects (of both terrestrial and extraterrestrial origins), probing into dynamics of targeted chemicals with ultra-high sensitivity, and local editing and inspections of semiconductor devices (often supporting intelligent process controls). With decades of remarkable developments, research interests continue to be steadily churned by evolving needs, especially around efficiently generating diverse ion species (across the periodic table), including complex molecular and cluster ions and ions at high charge states. Several parameters generally define the desirable beam characteristics, namely, high angular current intensity IΩ(~ tens of μA/sr), high beam brightness (reduced brightness of ~106 A m−2 sr−1 V−1 or higher), and low energy spread ΔE (~ 1 eV or lower). Intriguing physics issues around ionization schemes, ion confinements, transport and focusing of ions, stochastic space charge interactions, and above all, ion–target interactions are discussed. The parameters governing the characteristics of focused ion beams (or probes) and various dependencies (for example, scalings) are systematically laid down to understand the mechanisms for high-resolution probe formation and practical utilizations. The trends of research activities and developments are summarized, especially in the context of a wide range of emerging applications. An outlook for the future, especially for disruptive innovations, is discussed.