A simple liquid-phase laser fragmentation approach, resulting in the rapid transformation of CdSe microcrystals into colloidal quantum dots (QDs), is presented. Laser fragmentation is achieved by irradiating a CdSe suspension in dimethylformamide with intense infrared, picosecond laser pulses followed by surface passivation with oleylamine or different types of phosphines. The generated QDs reveal perfect colloidal stability preventing agglomeration and precipitation, and show characteristic QD absorption and fluorescence characteristics, whereas their emission properties strongly depend on the surface states and applied capping ligands. These QDs show distinct photoemission under 405-nm single-photon and 800-nm multi-photon excitations in the 560- to 610-nm spectral region corresponding to the QDs size of about 1.5–2 nm in diameter which is confirmed by transmission electron microscopy. © 2015, Springer Science+Business Media Dordrecht.