Multiple access and transmission enhancement in support of carrier aggregation techniques has been actively studied in the 3GPP LTEAdvanced standardization process of the nextgeneration mobile broadband communication systems. By means of carrier aggregation, users can access a total bandwidth of up to 100 MHz in order to meet the IMT-Advanced requirements. This article first introduces and compares several uplink multiple access schemes in LTE-Advanced standard. Technical challenges arising from the use of carrier aggregation is then addressed, with focus on reference signals design for uplink transmission. Meanwhile, various candidate options are summarized and compared in terms of their system performance, computational complexity, and design flexibility. The article further proceeds to investigate the link performance with carrier aggregation, taking into account the presence of frequency offset and fast fading in the uplink channel. Numerical results are also presented, which indicate that advanced signal processing algorithms should be further studied and optimized to ensure reliable operation of the 3GPP LTE-Advanced in high mobility.