The quest for a perfluorocarbon-based injectable oxygen carrier (PFC-OC) suitable for human use is still unresolved. Currently consensus exists on PFC-OCs composition (a PFC, an organic or artificial emulsifier, stabilizers, and electrolytes) and characteristics (oil in water emulsion, droplet size below 0.01 μm, blood-like viscosity). Challenges to manufacture PFC-OCs can be divided into four categories: equipment selection, definition of raw materials, definition of manufacturing process conditions and design of facilities. The main pieces of equipment are a microemulsifier, a particle size analyzer, and a Zeta potential analyzer, the latter required to assess emulsion stability. Droplet size, smallest sample size and cost are the most important criteria for microemulsifier selection. Minimal measurable droplet size and cost are the determining factors for particle size analyzer selection. Sample size and cost are the leading criteria for Zeta potential analyzer selection. Regarding raw materials, criteria for PFCs selection are biocompatibility, previous medical use, and reliable continuous commercial availability. Main criteria for selection of emulsifiers are previous medical use and biocompatibility. Criteria for stabilizers selection is based on their affinity with the active PFC and emulsifier In the manufacturing process the main decision is if the PFC-OC is going to be manufactured under sterile conditions, or it is going to be sterilized at the end of the process, with the latter probably affecting the stability of the emulsion. Design of facilities depends heavily on the selected manufacturing process and output volume. Once this challenges are solved, design of formulations can proceed, followed by in vitro and in vivo evaluation.