The pharmacokinetic comparison of phosphonic acid derivatives is based upon a survey of available literature on the whole group of compounds and on our own studies on fosfomycin. All three clinically used compounds, fosfomycin, fosmidomycin, and alafosfalin, are available for both oral and parenteral administration. The highest bioavailability is observed for the trometamol derivative of fosfomycin (37–44%); the calcium salt of fosfomycin is 2–2.5 times less absorbed and fosmidomycin has a bioavailability of 20–30%. The peak serum concentration of fosfomycin when given as the trometamol salt is about 2 times higher than the one reached with fosfomycin calcium or fosmidomycin. Urine recovery of unchanged drug is comparable after intravenous doses of fosfomycin and fosmidomycin, 80–95%, whereas the figure is only 10–20% for alafosfalin because it is extensively metabolized. After oral administration, urine recovery is highest for fosfomycin trometamol, 35–60%, compared to approximately 25% (range 18–29%) for fosfomycin calcium, 26% for fosmidomycin, and 6–17% for alafosfalin. The serum half-life of fosfomycin is 2–4 h (higher, up to 5.5 h, for some formulations of the calcium salt), 1.5–2.0 h for fosmidomycin, and about 1 h for alafosfalin. Thus, among available phosphonic acid derivatives and formulations, the trometamol derivative of fosfomycin has the most favourable characteristics. This applies to both bioavailability and urinary recovery, while at the same time the medium long half-life renders moderate fluctuation of concentrations whereby longer dosage intervals are possible. The serum protein binding of fosfomycin and fosmidomycin is below 3% (below 10% for alafosfalin); the penetration of fosfomycin is good to extravascular sites like muscle and connective tissue, cerebrospinal fluid, fetuses, amniotic fluid, prostatic secretion, and bone.