The development of sustainable bioprocesses based on the biological capabilities and potential phenotypic functionalities of photosynthetic (micro)organisms has recently been in the spotlight. This is due to their adaptability and promising standing to address challenges related to CO2 removal and bio-fixation, the biosynthesis of value-added organic compounds, wastewater treatment, and the production of third- and fourth-generation biofuels. Photoautotrophs (e.g., microalgae and cyanobacteria) are able to absorb (sun)light as a source of energy and CO2 from any CO2-containing gas stream as the building blocks to produce biomass and profitable biochemicals and release O2 (through H2O photolysis). At the core of these bioprocessing endeavors, the design and operation of photobioreactors serve as the central focus, particularly with respect to economic and sustainability factors. Both open (e.g., raceway ponds) and closed (e.g., flat panels and tubular apparatus) systems may be used for these very purposes. However, closed systems have a higher efficiency in terms of growth rate, productivity, protection against contamination, and produced biomass quality (e.g., lipid content). Among various possible configurations, column photobioreactors may be at the highest level of interest. Some of the most significant and considerable achievements regarding this category include appropriate access to the light source, opposite flow patterns, the controllable degree of turbulence and mixing, and providing optimal conditions for aeration and nutrient dispersion. However, significant challenges such as substantial capital investment, operating costs, and the need for precise operational conditions persist across a wide range of applications. This chapter examines and explores photobioreactors of this type.