Li-ion batteries are being widely used in planetary missions, based on their impressive performance characteristics, including high specific energy, long life, and the ability to operate over a wide temperature range. Custom large-format Li-ion cells were used in the early planetary missions, e.g., Mars Rovers, Mars Landers, and Mars and Jupiter Orbiters. At the same time, several other robotic missions have utilized and are planning to utilize commercial 18650 lithium-ion cells, e.g., Mars Express, Lunar Reconnaissance Orbiter, Europa Clipper, as well as human-rated astronaut Extra-Vehicular Activities. Interest in commercial 18650 lithium-ion cells for NASA missions has increased in recent years due to distinct advantages over custom large-format cells, including higher specific energy and energy density, enhanced safety and reliability, modularity and redundancy in the battery design, and simpler charge methodology. Multiple commercial 18650 cells are available which can provide a specific energy of ∼250 Wh∙kg−1 (20%–50% over custom cells) and a power density of ∼2 kW∙kg−1. Selected cell types with different chemistries and from multiple high-quality manufacturers, including the MJ1, M36, HG2 models from LG Chem; the 35E, 36 G and 30Q models from Samsung; the BJ and GA models from Sanyo/Panasonic; and the VC7 from Sony/Murata, were evaluated for their applicability in space applications. The performance tests included cycle life at different temperatures and depths of discharge, and high-power characterization at different temperatures; to supplement typical electrical measurements of voltage, capacity, and energy, Electrochemical Impedance Spectroscopy (EIS) was used to characterize the health of some cells on an ongoing basis. In addition, destructive physical analysis was carried out on these cells to analyze their electrode materials and correlate them with their performance characteristics. The demonstrated performance of several cells indicated their viability for further extensive space-qualification prior to their implementation in space missions.