New methods enable single-cell transcriptomics profiling of a complex tissue. (a) In single cell approaches, canonically, individual cells are first dissociated and then isolated by micropipette, automated cell sorting, or microfluidics-enabled capturing. Cellular RNAs are then amplified and sequenced. (b) The transcriptome of an individual cell can be determined by first photoactivating a TIVA-tag within that cell, allowing it to hybridize to cellular mRNAs. These mRNAs can then be specifically purified and sequenced by any RNA-seq method. (c) FISSEQ allows for RNA-Seq within the context of the cell by first fixing mRNA and then amplifying (by rolling circle amplification) and sequencing by the SOLiD technology. FISSEQ: fluorescent in situ RNA sequencing; IVT: in vitro transcription; PCR, polymerase chain reaction; RNA-seq: RNA sequencing; RT: reverse transcription; SOLiD; sequencing by oligonucleotide ligation and detection; TIVA: transcriptome in vivo analysis.