Fluorinated materials play an essential role in modern industry and technology, and their importance is expected to grow even more in the near future. Unfortunately, their practical application often requires dispersion by means of fluorinated surfactants, which raised huge environmental and toxicity concerns due to their long-lasting persistence in the environment and high tendency to accumulate in animals and humans. A greener and more sustainable strategy towards the replacement of synthetic fluorosurfactants is offered by the use of amphiphiles of biological origin. Among them, phospholipids have been the most widely exploited as emulsifiers of fluorous compounds. Some interesting examples were also reported using amphiphilic proteins, in particular fungal hydrophobins, as biosurfactants and coating agents for fluorinated substrates. This perspective offers an overview of the main natural surfactants currently used in fluorine chemistry, focusing in particular on two main application areas: (i) fluorous oil-in-water emulsions and gas microbubbles for biomedical imaging and drug delivery, and (ii) coating and functionalization of solid fluorinated surfaces.