Given the increasing global demand for rare earth elements (REE), prospects for REE recovery from both traditional and non-traditional sources have been a focus of intense interest. Many have noted the need for ecologically sustainable alternatives to conventional pyrometallurgical and hydrometallurgical methods to recover REE. Among the newer approaches that have garnered recent interest are those that rely on microbiological processes or microbiologically produced reagents to recover the rare earths. Biological approaches can often avoid many of the environmental and or safety hazards associated with the corrosive (e.g., strong acids) or toxic chemicals (e.g., organic solvents) often used in hydrometallurgy as well as costs related to the high energy, reagent and capital requirements and potential air emissions associated with pyrometallurgy. Microbial processes are considered environmentally friendly because they are “natural”, although opportunities also exist to improve on native capabilities by the application of synthetic biology. In this chapter we will focus on some important factors that have not been as widely discussed but which should be considered in planning actual deployment of biological approaches for recovery and purification of rare earths, drawing on some of our own experience for examples. In particular we will focus on geochemical and biogeochemical constraints posed by the feedstocks from which REE may be extracted, for both bioleaching and biosorption, and point out the importance of aqueous equilibrium modeling as a tool for interpreting results and supporting design of biological recovery methods. We will also discuss some important cost factors for REE recovery that are specific to biological processes.