Fluorescent proteins have proven to be a useful tool for bio-imaging, protein interaction, sensing and chemical detection. Red fluorescent proteins have emissions above 580nm which makes them an ideal protein for in vivo bio-imaging. The mRFP protein with emissions at 607nm is one of the few monomeric far red-shifted proteins that are useful for tag-fusion expression purposes. DsRed is an obligate tetramer that has emissions at 590nm while HcRed has emissions reaching 615nm but it is disadvantaged as it is a dimeric protein which negates its use as a tag fusion expression partner. The maturation of the red fluorescent proteins follows a series of oxidative and dehydration steps after folding to form the mature chromophore that consist of a series of conjugated bonds that permit fluorescence. The mRFP was synthesized, mutated and screened for improved functionality. The applications of red fluorescent proteins for resonance energy transfer will be reported.