The feedstocks for are the C₅ naphtha cracking fractions from which it can be isolated by extractive distillation or, more recently, by distillation as an azeotrope with n-pentane.

The direct isolation of isoprene from corresponding fractions of naphtha cracked products has the advantage that isoprene can be obtained without additional synthetic steps. This method can be economical, especially since the isoprene concentration in a typical C₅ fraction from more severe cracking can comprise from 14 to 23 wt%. The other components of the C₅ fraction are pentanes, cyclopentadiene/diclopentadiene, piperylene and pentenes.

Various butadiene isolation processes can be modified for isoprene, including extractive distillation with N-methylpyrrolidone (BASF), dimethylformamide (Nippon Zeon), or acetonitrile (Shell, Goodrich-Arco). Commercial units - chiefly in Japan and the United States - have isoprene capacities as large as 30000 tonnes per year.

Goodyear has developed a fractional distillation process using the C₅ fraction from a steam cracker in which isoprene is recovered as an azeotrope with n-pentane. Isoprene can be selectively reacted from this mixture, by polymerization for example. Commercial application of this technology, characterized by its low energy requirements, is not yet widespread.

Dehydrogenation processes with isopentane and isopentenes are used mainly in the USA. The feedstocks are the C₅ fractions from catalytic cracking processes which are introduced as mixtures to the dehydrogenation. Due to their greater reactivity, the alkenes are dehydrogenated before the alkanes. The subsequent purification, especially the separation of 1,3-pentadiene (piperylene), is very involved. Therefore, Shell first separates the 2-methylbutenes from the rest of the C₅ products in a so-called Sinclair extraction with 65% H₂SO₄. The acid initially isomerizes the mixture of the 2-methylbutenes mainly to 2-methyl-2-butene, and then adds to form the sulfuric acid ester:

The ester is then split at 35 °C and the C₅ olefin is extracted. The required dehydrogenation to isoprene is similar to processes for butadiene. The Shell process employs a Fe₂O₃-Cr₂O₃-K₂CO₃ catalyst at 600 °C, and achieves yields of about 85%. Pure isoprene (99.0-99.5 wt%) is isolated by extractive distillation with acetonitrile. Isoprene plants using this process are operated by Shell, ArcO and Exxon.

In the CIS, isoprene is manufactured in three plants (total capacity 180000 tonnes per year) by dehydrogenation of isopentene in a process which has not been disclosed in detail.